Table 3. In-silico mutation experiments for validation.
No. | Species | Organisms | Exp. | Experimental effects | Effects in our models |
1. | Mad2 | H. s. | D | -Impaired MSAC [32] | - MSAC fails to arrest |
Mad2 | M. | D | -Unable to arrest [72] | & no Cdc20 sequestering. | |
Mad2 | H. s. & M. | D | -Defective MSAC [73] | - [APC:Cdc20] very high. | |
Mad2 | H. s. | D | -Unable to bind Cdc20 or Mad1 [74]. More refs.: [31], [40], [108] [1], [34], [109]-[111]. | ||
2. | Mad2 | H.s. | O | -Activates the MSAC [25] | -Activates the MSAC |
Mad2 | S.p. | O | -Blocks mitosis [90] | & full Cdc20 sequestering. -[APC:Cdc20] very low. | |
3. | Mad1 | H.s. | D | - MSAC inactivation & aneuploidy [75]. | - MSAC fails to arrest & no Cdc20 sequestering. |
Mad1 | S.p. | D | - cell death [76]. More refs.: [77]-[79]. | -[APC:Cdc20] very high. | |
4. | BubR1 | H.s. | D | -Reduced MSAC function, Reduced MSAC binding to Cdc20:C-Mad2 [47]. | -MSAC fails to arrest. |
-[APC:Cdc20] very high. | |||||
BubR1 | M. | D | -Increased polyploidy [82]. More refs.: [83], [84]. | ||
5. | Bub3 | M. | D | -Fails to arrest [80], [81]. | -MSAC fails to arrest. |
-[APC:Cdc20] very high. | |||||
6. | Cdc20 | S.c. | O | -Allows cells with a depolymerized spindle or damaged DNA to leave mitosis [91]. | -MSAC fails to arrest. |
-[APC:Cdc20] very high. | |||||
-Impairment MSAC and aneuploidization in oral cancer [112]. | |||||
7. | Cdc20 | H.s. | D | -Reduced binding to Mad2, selective disruption from Mad2 [85]. | - blocks mitosis. |
-[APC:Cdc20] very low. | |||||
Cdc20 | S.p. | D | -Arrest in metaphase [113]. | ||
8. | Bub1 | Drosophila | Inh. | -Chromosome missegregation [86]. | -MSAC fails to arrest. |
-[APC:Cdc20] very high. | |||||
Bub1 | H.s. | Inh. | -Disruption of Bub3 localization, disruption of Bub3 binding to BubR1 [81]. | ||
9. | Aurora B | Xenopus | Inh. | -Overriding the MSAC function, perturbs MTs dynamics [87]. | -MSAC fails to arrest. |
-[APC:Cdc20] very high. | |||||
Aurora B | S.c. | Inh. | -Unregulated MTs, | ||
- MSAC fails to arrest [88], [89] | |||||
10. | APC (units) Cdc26, apc9 Cdc6,doc1 | S.p. | D | -Disruption of complex association [92], [93], More refs.: [114]. | -Activates the MSAC. |
-[APC:Cdc20] very low. |
Abbreviations: D for deletion or knockdown experiments, O for over-expression experiments, and Inh. for inhibition; S.c., Saccharomyces cerevisiae; S.p., Schizosaccharomyces pombe; H. s., Homo sapiens(Human); and M., Murine.